Skip to main content
Log in

Invasion and metastasis

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

The invasive character of squamous cell carcinoma of the head and neck represents a major challenge to the clinician since most often these tumors require extensive surgical resection impairing important physiological functions including speech and swallowing. Additionally, in many cases costly reconstructive surgery is required to repair the adverse cosmetic effects of the resective surgery. Thus, there is an urgent need to understand the molecular mechanism(s) which underlie the local and regional spread of this disease. Since the ability of tumor cells to invade into surrounding structures requires hydrolytic action much effort has been spent on identifying the hydrolases involved in this process. Some of the enzymes which have been implicated in the spread of head and neck cancer include the urokinase-type plasminogen activator and several members of the collagenase family such as type I and IV collagenases and the stromelysins synthesized either by the tumor cells or in the surrounding fibroblasts. More recent studies have addressed the mechanism(s) by which these hydrolases are overexpressed in invasive cancer. In the tumor cells themselves, work has focused on defining the transcriptional requirements for enzyme synthesis and addressing how the appropriate transcription factors are activated by signal transduction pathways. In contrast, where the hydrolases (e.g. stromelysin-2 and stromelysin-3) are produced by the fibroblasts, current investigations are directed at identifying tumor-derived growth factors which lead to the inducible expression of the enzymes in the stromal cells. The ultimate goal of these studies is to develop novel therapeutic interventions which decrease the invasive capacity of head and neck cancer leading to longer survival times and enhanced quality of life for patients afflicted with this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Tryggvason K, Hoyhtya M, Salo T: Proteolytic degradation of extracellular matrix in tumor invasion. Biochim Biophys Acta 907: 191–217, 1987

    Google Scholar 

  2. Hirota J, Yoneda K, Osaki T: Basement membrane type IV collagen in oral squamous cell carcinoma. Head and Neck 12: 400–405, 1990

    Google Scholar 

  3. Robbins KC, Summaria L, Hsieh B, Shah R: The peptide chains of human plasmin. J Biol Chem 242: 2333–2342, 1967

    Google Scholar 

  4. Liotta L, Goldfarb R, Brundage R, Siegel G, Terranova V, Garbisa S: Effect of plasminogen activator (urokinase), plasmin, and thrombin on glycoprotein and collagenous components of basement membrane. Cancer Res 41: 4629–4636, 1981

    Google Scholar 

  5. Salo T, Liotta L, Keski-Oja J, Turpeenniemi-Hujanen T, Tryggvason K: Secretion of basement collagen degrading enzyme and plasminogen activator by transformed cells-Role in metastasis. Int J Cancer 30: 669–673, 1982

    Google Scholar 

  6. Ossowski L, Reich E: Antibodies to plasminogen activator inhibit human tumor metastatis. Cell 35: 611–619, 1983

    Google Scholar 

  7. Yu H, Schultz R: Relationship between secreted urokinase plasminogen activator activity and metastatic potential in murine B16 cells transfected with human urokinase sense and antisense genes. Cancer Res 50: 7623–7633, 1991

    Google Scholar 

  8. Achbarou A, Kaiser S, Tremblay G, Ste-Marie L, Brodt P, Goltzman D, Rabbani SA: Urokinase overproduction results in increased skeletal metastasis by prostate cancer cells in vivo. Cancer Res 54: 2372–2377, 1994

    Google Scholar 

  9. Sappino A, Belin D, Huarte J, Hirschel-Scholz S, Saurat J, Vassalli J: Differential protease expression by cutaneous squamous and basal cell carcinomas. J Clin Invest 88: 1073–1079, 1991

    Google Scholar 

  10. Miller SJ, Jensen PJ, Dzubow LM, Lazarus GS: Urokinase plasminogen activator is immunocytochemically detectable in squamous cell but not basal cell carcinomas. J Invest Dermatology 98: 351–358, 1992

    Google Scholar 

  11. Clayman G, Wang SW, Nicolson GL, El-Naggar A, Mazar A, Henkin J, Blasi F, Goepfert H, Boyd D: Regulation of urokinase-type plasminogen activator expression in squamous cell carcinoma of the oral cavity. Int J Cancer 54: 73–80, 1993

    Google Scholar 

  12. Bernhard EJ, Muschel RJ, Hughes EN: Mr 92,000 gelatinase release correlates with the metastatic phenotype in transformed rat embryo cells. Cancer Res 50: 3872–3877, 1990

    Google Scholar 

  13. Bernhard EJ, Gruber SB, Muschel RJ: Direct evidence linking expression of matrix metalloproteinase 9 (92-kDa gelatinase/collagenase) to the metastatic phenotype in transformed rat embryo cells. Proc Natl Acad Sci USA 91: 4293–4297, 1994

    Google Scholar 

  14. Wilhelm SM, Collier IE, Marmer BL, Eisen AZ, Grant G, Goldberg G: SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. Degrades type IV collagen. Activation leads to removal of 73 amino acids. Contains zinc-binding domain and fibronectin domain. J Biol Chem 264: 17213–17221, 1989

    Google Scholar 

  15. Goldberg G, Strongin A, Collier IE, Genrich T, Marmer BL: Interaction of 92-kDa type IV collagenase with the tissue inhibitor of metalloproteinases prevents dimerization, complex formation with interstitial collagenase, and activation of the proenzyme with stromelysin. J Biol Chem 267: 4583–4591, 1992

    Google Scholar 

  16. Nakajima M, Welch DR, Wynn DM, Tsuruo T, Nicolson GL: Serum and plasma Mr 92,000 progelatinase levels correlate with spontaneous metastasis of rat 13762NF mammary adenocarcinoma. Cancer Res 53: 5802–5807, 1993

    Google Scholar 

  17. Bernhard EJ, Hagner B, Wong C, Lubenski I, Muschel RJ: The effect of E1A transfection on MMP-9 expression and metastatic potential. Int J Cancer 60: 718–724, 1995

    Google Scholar 

  18. Pyke C, Ralkiaer E, Huhtala P, Hurskainen T, Dano K, Tryggvason K: Localization of messenger RNA for Mr 72,000 and 92,000 type IV collagenase in human skin cancers by in situ hybridization. Cancer Res 52: 1336–1341, 1992

    Google Scholar 

  19. Juarez C, Clayman G, Nakajima M, Tanabe K, Saya H, Nicolson GL, Boyd D: Role and regulation of 92 kDa type IV collagenase (MMP-9) in invasive squamous cell carcinoma of the oral cavity. Int J Cancer 54: 73–80, 1993

    Google Scholar 

  20. Garbisa S, Scagliotti G, Di Francesco C, Caenazzo C, Onisto M, Micela M, Stetler-Stevenson WG, Liotta L: Correlation of serum metalloproteinase levels with lung cancer metastasis and response to therapy. Cancer Res 52: 4548–4549, 1992

    Google Scholar 

  21. Frisch SM, Reich R, Collier IE, Genrich LT, Martin G, Goldberg G: Adenovirus E1A represses protease gene expression and inhibits metastasis of human tumor cells. Oncogene 5: 75–83, 1990

    Google Scholar 

  22. Watson SA, Morris TM, Robinson G, Crimmin MJ, Brown PD, Hardcastle JD: Inhibiton of organ invasion by the matrix metalloproteinase inhibitor batimastat (BB-94) in two human colon carcinoma metastasis models. Cancer Res 55: 3629–3633, 1995

    Google Scholar 

  23. Huhtala P, Chow L, Tryggvason K: Structure of the human type IV collagenase gene. J Biol Chem 265: 11077–11082, 1990

    Google Scholar 

  24. Collier IE, Bruns GAP, Goldberg GI, Gerhard DS: On the structure and chromosome location of the 72- and 92-kDa human type IV collagenase genes. Genomics 9: 429–434, 1991

    Google Scholar 

  25. Overall CM, Wrana JL, Sodek J: Transcriptional and posttranscriptional regulation of 72kDa gelatinase/type IV collagenase by transforming growth factor-beta in human fibroblasts. J Biol Chem 266: 14064–14071, 1991

    Google Scholar 

  26. Okada A, Belloco J, Rouyer N, Chenard M, Rio M, Chambon P, Basset P: Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci USA 92: 2730–2734, 1995

    Google Scholar 

  27. Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, Seiki M: A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature 370: 61–65, 1994

    Google Scholar 

  28. Matrisian LM: The matrix-degrading metalloproteinases. BioEssays 14: 445–463, 1992

    Google Scholar 

  29. Muller D, Breathnach R, Engelmann A, Millon R, Bronner G, Flesch H, Dumont P, Eber M, Abecassis J: Expression of collagenase-related metalloproteinase genes in human lung or head and neck tumours. Int J Cancer 48: 550–556, 1991

    Google Scholar 

  30. Gray ST, Wilkins RJ, Yun K: Interstitial collagenase gene expression in oral squamous cell carcinoma. American Journal of Pathology 141: 301–306, 1992

    Google Scholar 

  31. Muller D, Wolf C, Abecassis J, Millon R, Engelmann A, Bronner G, Rouyer N, Rio M, Eber M, Methlin G et al.: Increased stromelysin 3 gene expression is associated with increased local invasiveness in head and neck squamous cell carcinomas. Cancer Res 53: 165–169, 1993

    Google Scholar 

  32. Bejarano PA, Noekken ME, Suzuki K, Hudson BG, Nagase H: Degradation of basement membranes by human matrix metalloproteinase 3 (stromelysin). Biochem J 256: 413–419, 1988

    Google Scholar 

  33. Polette M, Clavel C, Muller D, Abecassis J, Binninger I, Birembaut P: Detection of mRNAS encoding collagenase I and stromelysin 2 in carcinomas of the head and neck by in situ hybridization. Invasion Metastasis 11: 76–83, 1991

    Google Scholar 

  34. Polette M, Clavel C, Birembaut P, De Clerck YA: Localization by in situ hybridization of mRNAs encoding stromelysin 3 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 in human head and neck carcinomas. Pathology Research and Practice 189: 1052–1057, 1993

    Google Scholar 

  35. Hollas W, Hoosein N, Chung LWK, Mazar A, Henkin J, Kariko K, Barnathan E, Boyd D: Expression of urokinase and its receptor in invasive and non-invasive prostate cancer cell lines. Thrombosis and Haemostasis 68: 662–666, 1992

    Google Scholar 

  36. Henderson BR, Tansey WP, Phillips SM, Ranshaw IA, Kefford RE: Transcriptional and posttranscriptional activation of urokinase plasminogen activator gene expression in metastatic tumor cells. Cancer Res 52: 2489–2496, 1992

    Google Scholar 

  37. Nanbu R, Menoud P, Nagamine Y: Multiple instability-regulating sites in the 3' untranslated region of the urokinasetype plasminogen activator mRNA. Mol Cell Biol 14: 4920–4928, 1995

    Google Scholar 

  38. Sato H, Seiki M: Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene 8: 395–405, 1993

    Google Scholar 

  39. Huhtala P, Tuuttila A, Chow L, Lohi J, Keski-Oja J, Tryggvason K: Complete structure of the human gene for 92-kDa type IV collagenase. J Biol Chem 266: 16485–16490, 1991

    Google Scholar 

  40. Lyons J, Birkedal-Hansen H: Interleukin-1b and transforming growth factor/EGF induce expression of Mr 95,000 type IV collagenase/gelatinase and interstitial fibroblast-type collagenase by rat mucosal keratinocytes. J Biol Chem 268: 19143–19151, 1993

    Google Scholar 

  41. Sato H, Kita M, Seiki M: v-src activates the expression of 92-kDa type IV collagenase through the AP-1 site and the GT Box homolgous to retinoblastoma control elements. J Biol Chem 268: 23460–23468, 1993

    Google Scholar 

  42. Riccio A, Grimaldi G, Verde P, Sebastio G, Boast S, Blasi F: The human urokinase plasminogen activator gene and its promoter. Nucl Acids Res 13: 2759–2771, 1985

    Google Scholar 

  43. Verde P, Boast S, Franze A, Robbiati F, Blasi F: An upstream enhancer and a negative element in the 5′ flanking region of the human urokinase plasminogen activator gene. Nucl Acids Res 16: 10699–10715, 1988

    Google Scholar 

  44. Von der Ahe D, Pearson D, Nagamine Y: Macromolecular interaction on a cAMP responsive region in the urokinasetype plasminogen activator gene: a role of protein phosphorylation. Nucleic Acids Research 18: 1991–1999, 1990

    Google Scholar 

  45. Menoud P, Matthies R, Hofsteenge J, Nagamine Y: Purification and cDNA cloning of a transcription factor which functionally cooperates within a cAMP regulatory unit in the porcine uPA gene. Nucleic Acids Research 21: 1845–1852, 1993

    Google Scholar 

  46. Nerlov C, Rorth P, Blasi F, Johnsen M: Essential AP-l and PEA3 binding elements in the human urokinase enhancer display cell type-specific activity. Oncogene 6: 1583–1593, 1991

    Google Scholar 

  47. Verde P, Stoppelli MP, Galeffi P, Di Nocera P, Blasi F: Identification and primary sequence of an unspliced human urokinase poly (A+) RNA. Proc Nat Acad Sci USA 81: 4727–4731, 1984

    Google Scholar 

  48. Kasai S, Arimura H, Nishida M, Suyama T: Primary structure of single-chain pro-urokinase. J Biol Chem 260: 12382–12389, 1985

    Google Scholar 

  49. Grimaldi G, Di Fiore P, Locatelli EK, Falco J, Blasi F: Modulation of urokinase plasminogen activator gene expression during the transition from quiescent to proliferative state in normal mouse cells. EMBO J 5: 855–861, 1986

    Google Scholar 

  50. Rossi P, Grimaldi P, Blasi F, Geremia R, Verde P: Folliclestimulating hormone and cyclic AMP induce transcription from the human urokinase promoter in primary cultures of mouse Sertoli cells. Molecular Endocrinology 4: 940–946, 1990

    Google Scholar 

  51. Rorth P, Nerlov C, Blasi F, Johnsen M: Transcription factor PEA3 participates in the induction of urokinase plasminogen activator transcription in murine keratinocytes stimulated with epidermal growth factor or phorbolester. Nucleic Acids Research 128: 5009–5017, 1990

    Google Scholar 

  52. Nerlov C, De Cesare D, Pergola F, Carracciolo A, Blasi F, Johnsen M, Verde P: A regulatory element that mediates co-operation between a PEA3-AP-l element and AP-l site is required for phorbol ester induction of urokinase enhancer activity in HepG2 hepatoma cells. EMBO J 11: 4573–4582, 1992

    Google Scholar 

  53. Hansen SK, Nerlov C, Zabel U, Verde P, Johnsen M, BAeuerle A, Blasi F: A novel complex between the p65 subunit of NF-kB and c-Rel binds to a DNA element involved in the phorbol ester induction of the human urokinase gene. EMBO J 11: 205–213, 1992

    Google Scholar 

  54. De Cesare D, Vallone D, Caracciolo A, Sassone-Corsi P, Nerlov C, Verde P: Heterodimerization of c-jun with ATF-2 and c-fos is required for positive and negative regulation of the human urokinase enhancer. Oncogene 11: 365–376, 1995

    Google Scholar 

  55. Kolesnick R, Golde DW: The spingomyelin pathway in tumor necrosis factor and interleukin-l signaling. Cell 77: 325–328, 1994

    Google Scholar 

  56. Karin M: Signal transduction from the cell surface to the nucleus through the phosphorylation of transcription factors. Curr Opin Cell Biol 6: 415–424, 1994

    Google Scholar 

  57. Pepper MS, Matsumoto K, Nakamura T, Orei L, Montesano R: Hepatocyte growth factor increases urokinasetype plasminogen activator (u-PA) and u-PA receptor expression in Madin-Darby canine kidney epithelial cells. J Biol Chem 267: 20493–20496, 1992

    Google Scholar 

  58. Stacey DW, Roudebush M, Day R, Mosser SD, Gibbs JB, Feig LA: Dominant inhibitory ras mutants demonstrate the requirement for ras activity in the action of tyrosine kinase oncogenes. Oncogene 6: 2297–2304, 1991.

    Google Scholar 

  59. Graziani A, Gramaglia D, Zonca P, Comoglio PM: Hepatocyte growth factor/scatter factor stimulates the Ras-guanine nucleotide exchanger. J Biol Chem 268: 9165–9168, 1993

    Google Scholar 

  60. Sasaoka T, Langlois WJ, Leitner JW, Draznin B, Olefsky JM: The signaling pathway coupling epidermal growth factor receptors to activation of p21ras. J Biol Chem 268: 32621–32625, 1994

    Google Scholar 

  61. Kuzumaki N, Ggiso Y, Oda A, Fujita H, Suzuki H, Sato C, Mullauer L: Resistance to oncogenic transformation in revertant R1 of human ras-transformed NIH 3T3 cells. Mol Cell Biol 9: 2258–2263, 1989

    Google Scholar 

  62. Huang W, Alessandrini A, Crews CM, Erikson RL: Raf-l forms a stabke complex with Mekl and activates Mekl by serine phosphorylation. Proc Natl Acad Sci USA 90: 10947–10951, 1993

    Google Scholar 

  63. Minden A, Lin A, McMahon M, Lange-Carter C, Derijard B, Davis RJ, Johnson GL, Karin M: Differential activation of ERK and JNK mitogen-activated protein kinases by rat-l and MEKK. Science 266: 1719–1722, 1994

    Google Scholar 

  64. Bruder JT, Heidecker G, Rapp UR: Serum-, TPA-, and Rasinduced expression from Ap-l/Ets-driven promoters requires Raf-l kinase. Genes and Development 6: 545–556, 1992

    Google Scholar 

  65. Kyriakis JM, App H, Zhang X, Banerjee P, Brautigan DL, Rapp UR, Avruch J: Raf-l activates MAP kinase-kinase. Nature 358: 417–420, 1992

    Google Scholar 

  66. Crews CM, Alessandrini A, Erikson RL: The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product. Science 258: 478–480, 1992

    Google Scholar 

  67. Gille H, Sharrocks AD, Shaw PE: Phosphorylation of transcription factor p62tcf by MAP kinase stimulates ternary complex formation at c-fos promoter. Nature 358: 414–417, 1992

    Google Scholar 

  68. Sozeri O, Vollmer K, Liyanage M, Frith D, Kour G, Mark GE, Stabel S: Activation of the c-raf protein kinase by protein kinase C phosphorylation. Oncogene 7: 2259–2262, 1992

    Google Scholar 

  69. Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL, Karin M: Identification of a dual specificity kinase that activates the Jun Kinases and p38-Mpk2. Science 268: 286–290, 1995

    Google Scholar 

  70. Galang CK, Der CJ, Hauser CA: Oncogenic ras can induce transcriptional activation through a variety of promoter elements. including tandem c-Ets-2 binding sites. Oncogene 9: 2913–2921, 1994

    Google Scholar 

  71. Deng T, Karin M: c-Fos transcriptional activity stimulated by H-ras-activated protein kinase distinct from JNK and ERK. Nature 371: 171–175, 1995

    Google Scholar 

  72. Rodriguez-Viciana P, Warne PH, Dhand R, Vanhaesebroeck B, Gout I, Fry MJ, Waterfield MD, Downward J: Phosphatidylinositol-3-OH kinase as a direct target of ras. Nature 370: 527–532, 1994

    Google Scholar 

  73. Mansour SJ, Matten WT, Hermann AS, Candia JM, Rong S, Fukusawa K, Vande Woude GF, Ahn NG: Transformation of mammalian cells by constitutively active MAP kinase kinase. Science 265: 966–970, 1994

    Google Scholar 

  74. Bell SM, Connoly DC, Maihle NJ, Degen JL: Differential modulation of plasminogen activator gene expression by oncogene-encoded protein tyrosine kinases. Mol Cell Biol 13: 5888–5897, 1993

    Google Scholar 

  75. Domann FE, Levy JP, Birrer MJ, Bowden GT: Stable expression of a c-JUN deletion mutant in two malignant mouse epidermal cell lines blocks tumor formation in nude mice. Cell Growth and Differentiation 5: 9–16, 1994

    Google Scholar 

  76. Brown PH, Alani R, Preis LH, Szabo E, Birrer MJ: Stable expression of a c-JUN deletion mutant in two malignant mouse epidermal cell lines blocks tumor formation in nude mice. Oncogene 8: 877–886, 1993

    Google Scholar 

  77. Robbins DJ, Zhen E, Owaki H, Vanderbilt CA, Ebert D, Geppert TD, Cobb MH: Regulation and properties of extracellular signal-regulated protein kinases 1 and 2 in vitro. J Biol Chem 268: 5097–5106, 1993

    Google Scholar 

  78. Shin DM, Ro JY, Hong WK, Hittelman WN: Dysregulation of epidermal growth factor receptor expression in premalignant lesions during head and neck tumorigenesis. Cancer Res 54: 3153–3159, 1994

    Google Scholar 

  79. Grandis J, Tweardy DJ: Elevated levels of transforming growth factor a and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res 53: 3579–3584, 1993

    Google Scholar 

  80. Sturgis E, Sacks PG, Masui H, Mendelsohn J, Schanz SP: Effects of antiepidermal growth factor receptor antibody 528 on the proliferation and differentiation of head and neck cancer. Head and Neck Surgery 111: 633–643, 1994

    Google Scholar 

  81. Schechter AL, Hung M, Vaidyanathan L, Weinberg RA, Yang-Feng TL, Francke U, Ullrich A, Coussens L: The neugene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 229: 976–978, 1985

    Google Scholar 

  82. Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T, Toyoshima K: Similarity of protein encoded by the human c-erbB2 gene to epidermal growth factor. Nature 319: 230–234, 1986

    Google Scholar 

  83. Beckhardt RN, Kiyokawa N, Liu TJ, Hung M, El-Naggar A. Clayman GL: Neu oncogene in head and neck squamous cell carcinoma. Proceedings of the American Association for Cancer Research 35: 153, 1994

    Google Scholar 

  84. Bongiorno PF, Whyte RI, Lesser EJ, Moore JH, Orringer MB, Beer DG: Alterations of K-ras, p53, and erbB2/neu in human lung adenocarcinomas. Journal of Thoracic Cardiovascular Surgery 107: 590–595, 1994

    Google Scholar 

  85. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer. Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235: 177–182, 1987

    Google Scholar 

  86. Mitra AB, Murty VVVS, Pratap M, Sodhani P, Chaganti RSK: ERBB2 (HER2/neu) oncogene is frequently amplified in squamous cell carcinoma of the uterine cervix. Cancer Res 54: 637–639, 1994

    Google Scholar 

  87. Lacroix H, Iglehart JD, Skinner MA, Krauss MH: Overexpression of erbB2 or EGF-receptor proteins present in early stage mammary carcinoma is detected simultaneously in matched primary tumors and regional metastasis. Oncogene 4: 145–151, 1989

    Google Scholar 

  88. Yu D, Hung MC: Expression of activated ras neu oncogene is sufficient to induce experimental metastasis in 3T3 cells. Oncogene 6: 1991–1996, 1991

    Google Scholar 

  89. Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD, Muller WJ: Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci USA 89: 10578–10582, 1992

    Google Scholar 

  90. Hou L, Shi D, Zhang HZ, Hung MC, Ling D: Oral cancer progression an c-erbB-2/neu proto-oncogene expression. Cancer Letters 65: 215–220, 1992

    Google Scholar 

  91. Gohji K, Nakajima M, Fabra A, Bucana CD, von Eschenbach AC, Tsuruo T, Fidler IJ: Regulation of gelatinase production in metastatic renal cell carcinoma by organ-specific fibroblasts. Japanese Journal of Cancer Research 85: 152–160, 1994

    Google Scholar 

  92. Matsumoto K, Horikoshi M, Rikimaru K, Enomoto S: A study of an in vitro model for invasion of oral squamous cell carcinoma. J Oral Path Med 18: 498–501, 1989

    Google Scholar 

  93. Lengyel E, Gum R, Juarez J, Clayman G, Seiki M, Sato H, Boyd D: Induction of Mr 92.000 type IV collagenase expression in a squamous cell carcinoma cell line by fibroblasts. Cancer Res 55: 963–967, 1995

    Google Scholar 

  94. Hurwitz A, Dushnik M, Solomon H, Ben-Chetrit A, Finci-Yeheskel Z, Milwidsky A, Mayer M, Adashi EY, Yagel S: Cytokine-mediated regulation of rat ovarian function: interleukin-1 stimulates the accumulation of a 92-kilodalton gelatinase. Endocrinology 132: 2709–2714, 1993

    Google Scholar 

  95. Shima I, Sasaguri Y, Kusukawa J, Nakano R, Yamana H, Fufita H, Kakegawa T, Morimatsu M: Production of matrix metalloproteinase 9 (92-kDa gelatinase) by human oesophageal squamous cell carcinoma in response to epidermal growth factor. Br J Cancer 67: 721–727, 1993

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boyd, D. Invasion and metastasis. Cancer Metast Rev 15, 77–89 (1996). https://doi.org/10.1007/BF00049488

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00049488

Key words

Navigation